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CARM1 substrate identification

ABSTRACT: The goal of the project was global identification of CARM1 substrates. Arginine methylation landscapes were profiled and compared in wild type and CARM1 knockout cells to determine in vivo substrates of CARM1.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast Epithelium, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Evgenia Shishkova

LAB HEAD: Joshua J Coon

PROVIDER: PXD005871 | Pride | 2017-07-03

REPOSITORIES: Pride

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			Action	DRS
	13Apr2016_ES_CARM1_MCF7_NtermTrunc_1.raw	Raw
	13Apr2016_ES_CARM1_MCF7_NtermTrunc_2.raw	Raw
	13Apr2016_ES_CARM1_MCF7_NtermTrunc_3.raw	Raw
	13Apr2016_ES_CARM1_MCF7_NtermTrunc_4.raw	Raw
	19Apr2016_ES_Nterm_fr1.raw	Raw

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Publications

Global mapping of CARM1 substrates defines enzyme specificity and substrate recognition.

Shishkova Evgenia E Zeng Hao H Liu Fabao F Kwiecien Nicholas W NW Hebert Alexander S AS Coon Joshua J JJ Xu Wei W

Nature communications 20170524

Protein arginine methyltransferases (PRMTs) introduce arginine methylation, a post-translational modification with the increasingly eminent role in normal physiology and disease. PRMT4 or coactivator-associated arginine methyltransferase 1 (CARM1) is a propitious target for cancer therapy; however, few CARM1 substrates are known, and its mechanism of substrate recognition is poorly understood. Here we employed a quantitative mass spectrometry approach to globally profile CARM1 substrates in brea ...[more]

PMID: 28537268

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Gene expression profiles of CARM1 overexpression in MCF7

Project description:The goal of this study is to identify ERalpha-target genes affected by overexpression of the histone arginine methyltransferase CARM1 in breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 overexpressing MCF7 cell line where CARM1 is overexpressed by 2 fold to determine the created a Dox-inducible CARM1 overexpressing MCF7 cells for evaluation of the global effects of CARM1 on Eralpha-target gene expression. MCF7-tet-on-CARM1 clone 13 were treated under 4 conditions: DMSO; Dox; E2 (10nM); Dox+E2. In Dox+E2 condition, cells were pre-treated with Dox for 5 days before treating with E2 for 4 hours. 3 biological replicates were included and total of 12 samples were analyzed.

2011-06-01 | E-GEOD-26454 | biostudies-arrayexpress

Gene expression profiles of MCF7 with CARM1 knocked down

Project description:The goal of this study is to identify ERalpha-target genes affected by knocking down of the histone arginine methyltransferase CARM1 in MCF7 breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 knockingdown MCF7 cell line where CARM1 is decreased to 20% of endogeneous level to determine the created a Dox-inducible CARM1shRNA overexpressing MCF7 cells for evaluation of the global effects of CARM1 on ERalpha-target gene expression. MCF7-tet-on-CARM1shRNA clone 1 were treated under 4 conditions: DMSO; Dox; E2 (10nM); Dox+E2. In Dox+E2 condition, cells were pre-treated with Dox for 5 days before treating with E2 for 4 hours. 3 biological replicates were included and total of 12 samples were analyzed.

2011-06-01 | E-GEOD-26259 | biostudies-arrayexpress

CARM1 Methylates MED12 to Regulate its RNA Binding Ability

Project description:The coactivator-associated arginine methyltransferase (CARM1) functions as a regulator for transcription, splicing and chromatin regulation by methylating a diverse array of substrates. In this study, we used CARM1 substrate antibodies to perform immunoprecipitation coupled with mass spectrometry (IP-MS) in MEFs and identified Mediator Subunit 12 (MED12) as a novel substrate for CARM1. ChIP-seq analysis using CARM1, MED12 and H3R17me2a (represents ‘CARM1 activity’) antibodies revealed that MED12 targeted by CARM1 is recruited to the EREs (estrogen-responsive elements). Additionally, RT-PCR studies showed that the MED12R1899K mutation disrupting the methylation site reduced the expression of ER-target genes. Thus, MED12 methylation targets it to ER-specific enhancers and positively modulates transcription of Estrogen-driven genes.

2018-09-05 | GSE72848 | GEO

Histone arginine methyltransferase CARM1-mediated H3R26me2 is essential for morula-to-blastocyst transition in pigs

Project description:we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos

2021-05-06 | GSE173965 | GEO

CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [RNA-Seq]

Project description:CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers.

2018-03-02 | GSE95644 | GEO

CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [ChIP-Seq]

2018-03-02 | GSE95643 | GEO

CARM1 interacts and hypermethylates the NuRD chromatin remodeling complex to promote gene transcriptional activation and cell cycle progression

Project description:Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.

2024-07-17 | GSE209910 | GEO

CARM1 interacts and hypermethylates the NuRD chromatin remodeling complex to promote gene transcriptional activation and cell cycle progression

2024-07-17 | GSE209909 | GEO

CARM1 interacts and hypermethylates the NuRD chromatin remodeling complex to promote gene transcriptional activation and cell cycle progression

2024-07-17 | GSE208775 | GEO

Global tibialis anterior skeletal muscle transcript data from male Carm1 skm-/- (HSAcre Tg/0 x Floxed Carm1) and Carm1 skm+/+ mice (HSAcre 0/0 x Floxed Carm1) on a chow diet.

Project description:Transcript data from tibialis anterior muscle from male muscle-specific Coactivator-Associated Arginine Methyltransferase 1 (Carm1 ) knockout mice (Carm1 skm-/- ) and wild-type mice (Carm1 skm+/+) generated by using the Cre-loxP system (on a C57BL6J/129 background) with HSA-Cre mice (from Jackson laboratories). We used RNA-Seq to detail the effects of muscle-specific loss of Carm1 on the global program of gene expression in tibialis anterior muscle.

2022-08-24 | GSE189351 | GEO

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